Use of circulating tumor DNA in newly diagnosed DLBCL patients.
Authors: Sarah Tomassetti, Yazeed Samara, Katie LaBarbera, Xin Qing, Richa Rathore, Alexey Aleshin, Laron McPhaul
Journal: Journal of Clinical Oncology (2022)

e19552 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. With upfront treatment, 40% of patients relapse. Currently, treatment response and surveillance are monitored using positron emission tomography/computerized tomography (PET/CT). However, no study to date has shown significant improvement in outcomes in lymphoma patients using standard radiographic and clinical surveillance. Most often, relapses likely occur from minimal residual disease (MRD) below the detection of imaging. Thus, a subclinical biomarker to better monitor treatment response and surveillance is needed. Circulating tumor DNA (ctDNA) has emerged as a sensitive biomarker for detecting MRD. Here, we aimed to evaluate the utility of ctDNA as a biomarker for monitoring treatment response and surveillance in patients with lymphoma. Methods: ctDNA analysis using a personalized, tumor-informed assay (Signatera bespoke mPCR NGS assay) was performed on blood samples collected from 15 patients with newly diagnosed DLBCL who presented to Harbor-UCLA Medical Center in 2021. Blood samples were collected at diagnosis, prior to each cycle of therapy, and every 3 months thereafter for surveillance. The primary endpoint was the rate of ctDNA clearance during treatment and its correlation with radiological imaging. Secondary endpoints included ctDNA positivity rate during surveillance and its correlation with radiological imaging. Additional data collected included patient demographics, lymphoma characteristics, and treatment regimen. Results: Of the 15 patients included in this cohort, the median age was 54 years and the percentage of patients with stage 1, 2, 3, and 4 disease was 7%, 20%, 7% and 67%, respectively. A total of 7% had high risk IPI scores. Within this cohort, 80% received RCHOP and 20% received daREPOCH. ctDNA was detected in 93.3% (14/15) of patients at diagnosis, with levels ranging from 2-3,607 mean tumor molecules (MTM)/mL of plasm. Of the ctDNA+ patients, 6 (40%) patients had a complete response to initial therapy as assessed by post-treatment imaging. Longitudinal assessment of ctDNA after each cycle of therapy revealed concordance with radiological findings, where 2/6 cleared ctDNA after cycle 1, 4/6 cleared ctDNA after cycle 2, 5/6 cleared ctDNA after cycle 3, and 6/6 cleared ctDNA after cycle 4 of treatment. One patient had undetectable ctDNA after cycle 4, but had a Deauville score of 4 on post-treatment PET/CT and was referred to radiation. Of the 3 patients who remained ctDNA positive on longitudinal testing, all were confirmed to have primary refractory disease by imaging. Of the remaining patients, 1 patient died after daREPOCH cycle 1 and 3 patients are undergoing initial therapy. Conclusions: ctDNA may serve as an important biomarker to assess response to treatment and for surveillance in DLBCL patients. Further studies evaluating ctDNA use in the clinical setting are needed before its application in routine practice.